B-Interferon is a fibroblast-derived cytokine that exhibits antiviral, anti-proliferative and immunomodulatory effects on many cell types. Recombinant human B-interferon has proven effective in treating Multiple Sclerosis and has a current estimated worldwide market of $2.3 billion annually. We propose to create modified B-interferon proteins that can be administered less frequently, but with greater efficacy, than existing B-interferon products. During Phase I we identified sites in B-interferon that can be modified without affecting the protein's in vitro bioactivity. During Phase II, we will develop manufacturing processes to produce sufficient quantities of the modified B-interferon proteins for testing in animal disease models. In a clinical setting, the improved characteristics of the novel B-interferon proteins may reduce the amount of B-interferon required per patient, reduce toxicity, improve patient compliance and quality of life and result in considerable cost savings to patients and healthcare providers. B-Interferon is a member of a large family of structurally related growth factors and cytokines. Information gained from these studies will aid in creating long-acting versions of other members of this gene family for use in treating cancer, infectious disease and hematopoeitic disorders.